Bioinspired 3D Multilayered Shape Memory Scaffold with a Hierarchically Changeable Micropatterned Surface for Efficient Vascularization

How to achieve three-dimensional (3D) cell alignment and subsequent prompt tissue regeneration remains a great challenge. Here, inspired by the interior 3D architecture of native arteries, we develop a new 3D multilayered shape memory vascular scaffold with a hierarchically changeable micropatterned surface for vascularization. The shape memory function renders the implantation of the scaffold safe and convenient via minimally invasive surgery. By co-culturing endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) on the 3D multilayered structure, the inner monolayer, which has a square micropatterned surface, can promote EC adhesion and migration, resulting in a rapid endothelialization, and the outer multilayers, which have rectangular micropatterned surfaces, can induce a circumferential alignment of VSMCs. After implantation in the cervical artery of a New Zealand rabbit for 120 days, the graft developed a high capacity for modulating cellular 3D alignment, to generate a neonatal functional blood vessel with an endothelium layer in the inner layer and multilevel VSMC circumferential alignments in the outer layers.